Patients suffering from cardiovascular disease frequently use herbal medicines as a low-cost alternative to conventional, pharmacological treatment. American ginseng is a very commonly consumed herbal remedy for cardiovascular conditions and it is a putative antioxidant. Since oxidant-mediated injury is a known mechanism of acute and chronic cardiac dysfunction, these herbs could offer cardioprotective effects through attenuation of oxidant injury. Reactive oxygen species (ROS) are generated in two distinct scenarios: acute oxidant release in conditions such as ischemia/reperfusion (I/R) and ROS generation as signaling molecules in several biological processes. We propose to study the antioxidant effects of American ginseng, which could affect both these distinct roles of ROS. During conditions of acute oxidant stress, ROS are generated rapidly from several sites within the cardiomyocyte, resulting in injury to cellular constituents, dysfunction and cell death. Effective protection against such injury can be significantly improved only if exogenously administered antioxidants rapidly access the site of ROS generation. Since American ginseng contains active constituents (ginsenosides) that are endowed with chemical structures that allow rapid entry in the cells, the ginsenosides could scavenge free radicals resulting in protection against acute oxidant stress. American ginseng could also interact with ROS released within cardiomyocytes as signaling molecules in response to a variety of pathophysiological stimuli. Specific Aim 1 will study the protective effect of American ginseng when ROS are generated by simulated I/R in mouse cardiomyocytes, and Specific Aim 2 will examine American ginseng effects in attenuating ROS released in response to various stimuli and how the biological responses to redox-dependent processes are altered. Additionally, the antioxiant effects of extracts obtained from two parts of the American ginseng plant: the root and berry will be compared. Since the ginsenoside profile of the root extract and the berry extract differs significantly, we expect the antioxidant potential to differ. Our results could show that American ginseng extracts have a potential in treating cardiovascular disease. [unreadable] [unreadable]